The core histones H2A, H2B, H3 and H4, undergo various post-translational modifications, such as acetylation, methylation and phosphorylation. Core histone phosphorylation has roles in several biological responses, including transcription, mitosis, DNA repair and apoptosis. Histone phosphorylation may disrupt chromatin structure and/or provide a 'code' for the recruitment or occlusion of non-histone chromosomal proteins to chromatin. Among the better-characterized histone phosphorylation events are the phosphorylation of H3 at Ser10 and Ser 28, and the phosphorylation of the H2A variant H2A.X at Ser139. Much remains to be learned about the function of the many other core histone phosphorylation events in chromatin. This review provides an overview of the biological roles of core histone phosphorylation in mammalian cells.